Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection

Claire B Larmonier, J. K. Uno, Kang Moon Lee, T. Karrasch, D. Laubitz, R. Thurston, M. T. Midura-Kiela, Fayez K Ghishan, R. B. Sartor, C. Jobin, Pawel R Kiela

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Abstract

Curcumin (diferulolylmethane) demonstrates profound anti-inflammatory effects in intestinal epithelial cells (IEC) and in immune cells in vitro and exhibits a protective role in rodent models of chemically induced colitis, with its presumed primary mechanism of action via inhibition of NF-κB. Although it has been demonstrated effective in reducing relapse rate in ulcerative colitis patients, curcumin's effectiveness in Crohn's disease (CD) or in Th-1/Th-17 mediated immune models of CD has not been evaluated. Therefore, we investigated the effects of dietary curcumin (0.1-1%) on the development of colitis, immune activation, and in vivo NF-κB activity in germ-free IL-10-/- or IL-10-/-;NF-κBEGFP mice colonized with specific pathogen-free microflora. Proximal and distal colon morphology showed a mild protective effect of curcumin only at 0.1%. Colonic IFN-γ and IL-12/23p40 mRNA expression followed similar pattern (∼50% inhibition at 0.1%). Secretion of IL-12/23p40 and IFN-γ by colonic explants and mesenteric lymph node cells was elevated in IL-10-/- mice and was not decreased by dietary curcumin. Surprisingly, activation of NF-κB in IL-10-/- mice (phospho-NF-κBp65) or in IL-10-/-;NF-κBEGFP mice (whole organ or confocal imaging) was not noticeably inhibited by curcumin. Furthermore, we demonstrate that IL-10 and curcumin act synergistically to downregulate NF-κB activity in IEC and IL-12/23p40 production by splenocytes and dendritic cells. In conclusion, curcumin demonstrates limited effectiveness on Th-1 mediated colitis in IL-10-/- mice, with moderately improved colonic morphology, but with no significant effect on pathogenic T cell responses and in situ NF-κB activity. In vitro studies suggest that the protective effects of curcumin are IL-10 dependent.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume295
Issue number5
DOIs
StatePublished - Nov 2008

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Curcumin
Colitis
Interleukin-10
Interleukin-12
Crohn Disease
Epithelial Cells
Specific Pathogen-Free Organisms
Ulcerative Colitis
Dendritic Cells
Rodentia
Colon
Anti-Inflammatory Agents
Down-Regulation
Lymph Nodes
T-Lymphocytes
Recurrence
Messenger RNA

Keywords

  • Crohn's disease
  • Inflammatory bowel disease
  • NF-κB

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection. / Larmonier, Claire B; Uno, J. K.; Lee, Kang Moon; Karrasch, T.; Laubitz, D.; Thurston, R.; Midura-Kiela, M. T.; Ghishan, Fayez K; Sartor, R. B.; Jobin, C.; Kiela, Pawel R.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 295, No. 5, 11.2008.

Research output: Contribution to journalArticle

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abstract = "Curcumin (diferulolylmethane) demonstrates profound anti-inflammatory effects in intestinal epithelial cells (IEC) and in immune cells in vitro and exhibits a protective role in rodent models of chemically induced colitis, with its presumed primary mechanism of action via inhibition of NF-κB. Although it has been demonstrated effective in reducing relapse rate in ulcerative colitis patients, curcumin's effectiveness in Crohn's disease (CD) or in Th-1/Th-17 mediated immune models of CD has not been evaluated. Therefore, we investigated the effects of dietary curcumin (0.1-1{\%}) on the development of colitis, immune activation, and in vivo NF-κB activity in germ-free IL-10-/- or IL-10-/-;NF-κBEGFP mice colonized with specific pathogen-free microflora. Proximal and distal colon morphology showed a mild protective effect of curcumin only at 0.1{\%}. Colonic IFN-γ and IL-12/23p40 mRNA expression followed similar pattern (∼50{\%} inhibition at 0.1{\%}). Secretion of IL-12/23p40 and IFN-γ by colonic explants and mesenteric lymph node cells was elevated in IL-10-/- mice and was not decreased by dietary curcumin. Surprisingly, activation of NF-κB in IL-10-/- mice (phospho-NF-κBp65) or in IL-10-/-;NF-κBEGFP mice (whole organ or confocal imaging) was not noticeably inhibited by curcumin. Furthermore, we demonstrate that IL-10 and curcumin act synergistically to downregulate NF-κB activity in IEC and IL-12/23p40 production by splenocytes and dendritic cells. In conclusion, curcumin demonstrates limited effectiveness on Th-1 mediated colitis in IL-10-/- mice, with moderately improved colonic morphology, but with no significant effect on pathogenic T cell responses and in situ NF-κB activity. In vitro studies suggest that the protective effects of curcumin are IL-10 dependent.",
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AU - Karrasch, T.

AU - Laubitz, D.

AU - Thurston, R.

AU - Midura-Kiela, M. T.

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